Potential Mutations in Chinese Pathologic Myopic Patients and Contributions to Phenotype

Abstract

Purpose Pathologic myopia is a leading cause of visual impairment in East Asia. The aim of this study was to investigate the potential mutations in Chinese pathologic myopic patients and to analyze the correlations between genotype and clinical phenotype. Method One hundred and three patients with pathologic myopia and one hundred and nine unrelated healthy controls were recruited from Zhongshan Ophthalmic Center. Detailed clinical data, including ultra-widefield retinal images, measurements of best-corrected visual acuity, axial length, refractive error and ophthalmic examination results, were obtained. Blood samples were collected for high-throughput DNA targeted sequencing. Based on the screening results, phenotype-genotype correlations were analyzed. Results The study included 196 eyes of 103 patients (36 men and 67 women) with an average age of 52.19 (38.92 – 65.46) years, an average refractive error of -11.80 D (-16.38 – -7.22) and a mean axial length of 28.26 mm (25.79 – 30.73). The patients were subdivided into three groups: myopic chorioretinal atrophy (190 eyes of 101 patients), myopic choroidal neovascularization (17 eyes of 15 patients), and myopic traction retinopathy (71 eyes of 61 patients). Systematic analysis of variants in the 255 genes revealed six potential pathogenic mutations: PEX7, OCA2, LRP5 (rs545382, c.1647T>C), TSPAN12 (rs41623, c.765G>T), RDH5 (rs3138142, c.423C>T) and TTC21B (rs80225158, c.2385G>C). OCA2 mutations were primarily observed in patients with myopic traction maculopathy. Conclusion Genetic alterations contribute to various clinical characteristics in Chinese pathologic myopic patients. The study may provide new insights into the etiology of pathologic myopia and potential targets for therapeutic interventions.

Next-Generation Sequencing Screening of 43 Families with Non-Syndromic Early-Onset High Myopia: A Clinical and Genetic Study

“…observed the presence of a synonymous variant in this gene as pathological and the cause of EoHM presented by their patient. The authors suggested that although the variant does not alter the amino acid chain, the altered nucleotide can modify the secondary structure of the protein and can influence protein holding and gene expression [50]. PEX1 is a gene whose variants are related to defects in peroxisome biogenesis.…”

“…Variable expressivity and incomplete penetrance were found in this gene, which could be why the variant was also found in the father, who did not have a reported phenotype [66]. Chen S et al ( 2007) observed a family with ADOA, a novel OPA1 mutation, and a higher frequency of EoHM [50]. Nevertheless, the presence of EoHM in one family member without ADOA and OPA1 challenged the assumption that this mutation induced EoHM.…”

ATRA stimulates the expression of MMP2 and TGF-β2 via RDH5 in retinal pigment epithelium cells

“…In addition, as a key enzyme, retinol dehydrogenase 5 (RDH5) not only participates in the formation of 11-cis-retinol in the visual cycle, but also regulates the metabolism of RA/ATRA. Recent genetic studies have shown that RDH5 gene, mostly existed in retina, contributed to the pathogenesis of myopia [10][11][12].…”